Please use this identifier to cite or link to this item: https://doi.org/10.1089/scd.2012.0259
Title: Hypoxia-induced arterial differentiation requires adrenomedullin and notch signaling
Authors: Lanner, F.
Lee, K.L. 
Ortega, G.C.
Sohl, M.
Li, X.
Jin, S.
Hansson, E.M.
Claesson-Welsh, L.
Poellinger, L. 
Lendahl, U.
Farnebo, F.
Issue Date: 1-May-2013
Citation: Lanner, F., Lee, K.L., Ortega, G.C., Sohl, M., Li, X., Jin, S., Hansson, E.M., Claesson-Welsh, L., Poellinger, L., Lendahl, U., Farnebo, F. (2013-05-01). Hypoxia-induced arterial differentiation requires adrenomedullin and notch signaling. Stem Cells and Development 22 (9) : 1360-1369. ScholarBank@NUS Repository. https://doi.org/10.1089/scd.2012.0259
Abstract: Hypoxia (low oxygen) and Notch signaling are 2 important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increased Notch signaling in a process requiring the vasoactive hormone adrenomedullin. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, hypoxia-mediated upregulation of the arterial marker genes Depp, connexin40 (Gja5), Cxcr4, and Hey1 required Notch signaling. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxia-mediated induction of the arterial differentiation program. © 2013 Mary Ann Liebert, Inc.
Source Title: Stem Cells and Development
URI: http://scholarbank.nus.edu.sg/handle/10635/115764
ISSN: 15473287
DOI: 10.1089/scd.2012.0259
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